Abstract
Mammalian cells obtain folate, a water‐soluble vitamin, from their surroundings via transport across the plasma membrane. Internalized folate is compartmentalized between the cytoplasm and the mitochondria. Transport of folate into mitochondria is via the mitochondrial folate transporter (MFT). Chronic alcohol use disturbs folate physiology and metabolism, but little is known about its effect on transport into mitochondria. We addressed this issue using freshly isolated mitochondria from human‐derived liver HepG2 cells and from liver of rats chronically exposed to alcohol. Chronic exposure of HepG2 cells to alcohol and chronic alcohol feeding of rats led to a significant inhibition in mitochondrial folate uptake. This was associated with a significant reduction in level of expression of MFT protein, mRNA and heterogenous nuclear RNA. Chronic alcohol exposure also inhibited promoter activity of the human SLC25A32 gene (which encodes the hMFT). These findings show for the first time that chronic alcohol exposure/feeding significantly inhibit carrier‐mediated folate transport into mitochondria, and that the inhibition is exerted at the level of transcription of the SLC25A32 gene. [Supported by NIH and DVA grants].
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